Compounds similar to those of formula ##STR3## but solely in the form of racemates have been disclosed in J. Org. Chem. 27 3781 and 3788 (1963), Reeder et al., U.S. Pat. No. 3,371,085, and Japanese Patent 44/26302. These racemates are known to have sedative and tranquilizing effects.
However, the receptor theory of drug action, which teaches that pharmacologically active compounds act by interaction with a receptor which is a part of the cell affected by the action of a drug and is probably situated on the surface of the cell membrane, suggests that the racemic mixtures of compounds might not be as effective as a particular one of the optical isomers making up the racemic mixture.
According to the receptor theory of drug activity, the receptors are probably side chains or parts of the macromolecules which make up the cell surface layer. These side chains or parts of molecules have a definite, three-dimensional configuration, and can thus interact only with molecules possessing a complementary configuration. It is known that a relatively minor change in molecular shape can greatly alter the physiological effects of a chemical compound. This may be due to a change in the ability of the particular compound to bind itself to a particular receptor.
Indeed, there are cases known in which the S- and R- forms of optically active pharmacologically effective compounds are known to have different pharmacological effects. It cannot be predicted whether the enantiomers of optically active pharmacologically active compounds will have different effects in a given instance because the properties of the individual receptors are not known in detail, and the mechanisms by which pharmacologically active compounds exert their effects are also generally unknown. Nor can it be predicted which optical isomer will be active, nor how effective it will be in comparison to the optical isomer of opposite rotation or the racemic mixture. Of all presently known optically active drugs, the S- and R- configurations are found in almost equal numbers.
It is also very important to know what isomer is the active one in those cases where the enantiomers differ in effectiveness. Inactive forms dilute the active form, may be competitive antagonists, and may even have dangerous side effects. For example, the S- form of Ethambutole is an anti-tuberculous agent, while the R- form causes blindness in experimental animals, even at low dosages.
Therefore, one object of the present invention is to provide new optically active forms of 1-4 benzodiazepines.
Another object of the present invention is to provide a process for the preparation of solely a particular optically active form of 1-4 benzodiazepines.
A further object of the present invention is to provide compositions for administration of these useful compounds.